{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T11:21:39Z","timestamp":1790680899660,"version":"4.1.0"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T00:00:00Z","timestamp":1665964800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Macrophages from human and mouse skin share phenotypic and functional features, but remain to be characterized in pathological skin conditions. Skin-resident macrophages are known to derive from embryonic precursors or from adult hematopoiesis. In this report, we investigated the origins, phenotypes and functions of macrophage subsets in mouse and human skin and in cutaneous squamous cell carcinoma (cSCC) using the spectral flow cytometry technology that enables cell autofluorescence to be considered as a full-fledged parameter. Autofluorescence identifies macrophage subsets expressing the CD206 mannose receptor in human peri-tumoral skin and cSCC. In mouse, all AF\n                    <jats:sup>+<\/jats:sup>\n                    macrophages express the CD206 marker, a subset of which also displaying the TIM-4 marker. While TIM-4\n                    <jats:sup>-<\/jats:sup>\n                    CD206\n                    <jats:sup>+<\/jats:sup>\n                    AF\n                    <jats:sup>+<\/jats:sup>\n                    macrophages can differentiate from bone-marrow monocytes and infiltrate skin and tumor, TIM-4 identifies exclusively a skin-resident AF\n                    <jats:sup>+<\/jats:sup>\n                    macrophage subset that can derive from prenatal hematopoiesis which is absent in tumor core. In mouse and human, AF\n                    <jats:sup>+<\/jats:sup>\n                    macrophages from perilesional skin and cSCC are highly phagocytic cells contrary to their AF\n                    <jats:sup>-<\/jats:sup>\n                    counterpart, thus identifying autofluorescence as a\n                    <jats:italic>bona fide<\/jats:italic>\n                    marker for phagocytosis. Our data bring to light autofluorescence as a functional marker characterizing subsets of phagocytic macrophages in skin and cSCC. Autofluorescence can thus be considered as an attractive marker of function of macrophage subsets in pathological context.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2022.903069","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T03:33:55Z","timestamp":1665977635000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Autofluorescence identifies highly phagocytic tissue-resident macrophages in mouse and human skin and cutaneous squamous cell carcinoma"],"prefix":"10.3389","volume":"13","author":[{"given":"Pierre","family":"Bourdely","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciana","family":"Petti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sokchea","family":"Khou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aida","family":"Meghraoui-Kheddar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxane","family":"Elaldi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Cazareth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noushine","family":"Mossadegh-Keller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Boyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael H.","family":"Sieweke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Poissonnet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Sudaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronique M.","family":"Braud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabienne","family":"Anju\u00e8re","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,10,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1016\/j.immuni.2015.11.023","article-title":"Fetal HSCs versus EMP2s","volume":"43","author":"Sheng","year":"2015","journal-title":"Immunity"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.11.022","article-title":"The origin of tissue-resident macrophages: When an erythro-myeloid progenitor is an erythro-myeloid progenitor","volume":"43","author":"Perdiguero","year":"2015","journal-title":"Immunity"},{"key":"B3","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1126\/science.1219179","article-title":"A lineage of myeloid cells independent of myb and hematopoietic stem cells","volume":"336","author":"Schulz","year":"2012","journal-title":"Science"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-020-00849-2","article-title":"Does tissue imprinting restrict macrophage plasticity","volume":"22","author":"Guilliams","year":"2021","journal-title":"Nat Immunol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3909","article-title":"The prognostic landscape of genes and infiltrating immune cells across human cancers","volume":"21","author":"Gentles","year":"2015","journal-title":"Nat Med"},{"key":"B6","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1016\/j.immuni.2017.07.014","article-title":"Tissue-resident macrophages in pancreatic ductal adenocarcinoma originate from embryonic hematopoiesis and promote tumor progression","volume":"47","author":"Zhu","year":"2017","journal-title":"Immunity"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20180534","article-title":"Macrophages of distinct origins contribute to tumor development in the lung","volume":"215","author":"Loyher","year":"2018","journal-title":"J Exp Med"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20182124","article-title":"Specific targeting of CD163(+) TAMs mobilizes inflammatory monocytes and promotes T cell-mediated tumor regression","volume":"216","author":"Etzerodt","year":"2019","journal-title":"J Exp Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20081633","article-title":"Differential rates of replacement of human dermal dendritic cells and macrophages during hematopoietic stem cell transplantation","volume":"206","author":"Haniffa","year":"2009","journal-title":"J Exp Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.08.006","article-title":"Human dermal CD14(+) cells are a transient population of monocyte-derived macrophages","volume":"41","author":"McGovern","year":"2014","journal-title":"Immunity"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.10.004","article-title":"Origins and functional specialization of macrophages and of conventional and monocyte-derived dendritic cells in mouse skin","volume":"39","author":"Tamoutounour","year":"2013","journal-title":"Immunity"},{"key":"B12","doi-asserted-by":"publisher","first-page":"e0159961","DOI":"10.1371\/journal.pone.0159961","article-title":"Spectral cytometry has unique properties allowing multicolor analysis of cell suspensions isolated from solid tissues","volume":"11","author":"Schmutz","year":"2016","journal-title":"PloS One"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.08.043","article-title":"Multimodal analysis of composition and spatial architecture in human squamous cell carcinoma","volume":"182","author":"Ji","year":"2020","journal-title":"Cell"},{"key":"B14","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.immuni.2012.04.012","article-title":"Human tissues contain CD141hi cross-presenting dendritic cells with functional homology to mouse CD103+ nonlymphoid dendritic cells","volume":"37","author":"Haniffa","year":"2012","journal-title":"Immunity"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.04.007","article-title":"A unidirectional transition from migratory to perivascular macrophage is required for tumor cell intravasation","volume":"23","author":"Arwert","year":"2018","journal-title":"Cell Rep"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20171608","article-title":"Unveiling skin macrophage dynamics explains both tattoo persistence and strenuous removal","volume":"215","author":"Baranska","year":"2018","journal-title":"J Exp Med"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20180019","article-title":"Tissue-resident macrophages in the intestine are long lived and defined by Tim-4 and CD4 expression","volume":"215","author":"Shaw","year":"2018","journal-title":"J Exp Med"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1172\/JCI29919","article-title":"Critical roles for CCR2 and MCP-3 in monocyte mobilization from bone marrow and recruitment to inflammatory sites","volume":"117","author":"Tsou","year":"2007","journal-title":"J Clin Invest"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20161375","article-title":"Phagocytosis imprints heterogeneity in tissue-resident macrophages","volume":"214","author":"Gonzalez","year":"2017","journal-title":"J Exp Med"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.11.6770","article-title":"The mannose receptor mediates uptake of soluble but not of cell-associated antigen for cross-presentation","volume":"176","author":"Burgdorf","year":"2006","journal-title":"J Immunol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1016\/j.ccr.2013.09.014","article-title":"Low-dose irradiation programs macrophage differentiation to an iNOS(+)\/M1 phenotype that orchestrates effective T cell immunotherapy","volume":"24","author":"Klug","year":"2013","journal-title":"Cancer Cell"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2022.827987","article-title":"Using the autofluorescence finder on the Sony ID7000(TM) spectral cell analyzer to identify and unmix multiple highly autofluorescent murine lung populations","volume":"10","author":"Wanner","year":"2022","journal-title":"Front Bioeng Biotechnol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"ncomms11852","DOI":"10.1038\/ncomms11852","article-title":"Long-lived self-renewing bone marrow-derived macrophages displace embryo-derived cells to inhabit adult serous cavities","volume":"7","author":"Bain","year":"2016","journal-title":"Nat Commun"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1643","DOI":"10.1016\/j.cell.2020.05.007","article-title":"Interrogation of the microenvironmental landscape in brain tumors reveals disease-specific alterations of immune cells","volume":"181","author":"Klemm","year":"2020","journal-title":"Cell"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20151193","article-title":"Tumor macrophages are pivotal constructors of tumor collagenous matrix","volume":"213","author":"Afik","year":"2016","journal-title":"J Exp Med"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.11.011","article-title":"TIM-1 and TIM-4 glycoproteins bind phosphatidylserine and mediate uptake of apoptotic cells","volume":"27","author":"Kobayashi","year":"2007","journal-title":"Immunity"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20170829","article-title":"Developmental origin and maintenance of distinct testicular macrophage populations","volume":"214","author":"Mossadegh-Keller","year":"2017","journal-title":"J Exp Med"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12071860","article-title":"Tumor-associated neutrophils dampen adaptive immunity and promote cutaneous squamous cell carcinoma development","volume":"12","author":"Khou","year":"2020","journal-title":"Cancers (Basel)"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2021.03.018","article-title":"Cutaneous squamous cell carcinoma development is associated with a temporal infiltration of ILC1 and NK cells with immune dysfunctions","volume":"141","author":"Luci","year":"2021","journal-title":"J Invest Dermatol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.903069\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T03:33:58Z","timestamp":1665977638000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.903069\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,17]]},"references-count":29,"alternative-id":["10.3389\/fimmu.2022.903069"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.903069","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,17]]},"article-number":"903069"}}